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MIMM 324 > 34. Viral Vaccines > Flashcards

34. Viral Vaccines Flashcards

1
Q

what proportion of vaccines in Canada are against viruses?

A

2/3

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2
Q

what was the first vaccine?

A

Jenner’s smallpox vaccine

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3
Q

what is variolation?

A

liquid from smallpox given to healthy person and they become immune

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4
Q

what vaccine was developed after Jenner’s smallpox vaccine?

A

Pasteur’s rabies vaccine

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5
Q

how did Pasteur develop rabies vaccine?

A

Took rabbits with rabies virus –> dried material from lesions and gave to small child who survived

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6
Q

what type of vaccine did Pasteur discover

A

ATTENUATED

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7
Q

what vaccine was developed after Pasteur’s rabies vaccine?

A

yellow fever virus vaccine

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8
Q

how is yellow fever virus transmitted?

A

transmitted by mosquitos

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9
Q

how was the yellow fever virus vaccine developed?

A

passaged yellow fever in embryonated chicken eggs for >100 passages until less virulent

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10
Q

what type of vaccine is the yellow fever virus vaccine?

A

ATTENUATED

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11
Q

which is the only vaccine with Nobel prize for vaccine research?

A

yellow fever virus vaccine

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12
Q

after yellow fever virus, what vaccine was developed?

A

influenza vaccine

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13
Q

what type of vaccine is the influenza vaccine? how is it produced?

A

INACTIVATED –> grow virus in embryonated hen eggs, isolate, kill virus, vaccinate

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14
Q

successful development of yellow fever, polio, and influenza vaccines all benefit from:

A

successful development of yellow fever, polio, and influenza vaccines all benefit from ex vivo virus cultivation

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15
Q

what was the original poliovirus vaccine/ how was it made?

A

original: INACTIVATED

grow virus –> purify –> isolate virus –> inactivate

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16
Q

what types of poliovirus vaccines have been used?

A

1st: inactivated
2nd: oral attenuated
3rd: inactivated

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17
Q

why was the oral attenuated vaccine discontinued?

A

caused some cases of virus

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18
Q

what vaccine was after poliovirus?

A

MMR

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19
Q

what does MMR stand for?

A

Mumps, Measles, Rabies

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20
Q

what type of vaccine is Hepatitis B vaccine?

A

recombinant subunit vaccine

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21
Q

why was the Hepatitis B vaccine innovative?

A

just used the viral surface protein, not full virus –> therefore, only need parts of the virus as vaccine

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22
Q

what type of vaccine is the HPV vaccine?

A

VLP vaccine

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23
Q

why is the HPV vaccine unable to replicate?

A

just VLP –> no DNA so cannot replicate

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24
Q

what type of vaccine is rotavirus vaccine?

A

bovine-human reassortment

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25
Q

overall, 4 main types of vaccine

A
  1. inactivated
  2. protein
  3. VLP
  4. live attenuated
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26
Q

6 main “game-changing” events in vaccinology

A
  1. Jenner’s cowpox
  2. Pasteur’s discovery of attenuation
  3. Discovery of antitoxin/toxoids
  4. Cultivation of viruses ex vivo
  5. Recognition of polysaccharides in antigens that our bodies recognize as non-self
  6. Development of subunit vaccine
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27
Q

3 ways that vaccines work

A
  1. induce protective immunity
  2. establish immune memory
  3. prevent disease
28
Q

2 types of vaccine-induced antibodies

A
  1. mucosal IgA
  2. serum IgG
29
Q

role of mucosal IgA

A

protection at mucosal surfaces

30
Q

role of serum IgG

A

combat systemic infections and protection at mucosal surfaces

31
Q

what is the source of persistent antibody responses?

A

long-lived plasma cells

32
Q

where are long-lived plasma cells found?

A

MOST in bone marrow, some in spleen and draining in LN

33
Q

Purpose of memory B cells in vaccine-mediated immunity

A

act as 2nd line of defense

reduces disease severity AFTER infection

34
Q

do memory B cells block infection or maintain serum antibody levels?

A

NO –> only reduce disease severity

35
Q

role of memory T cells in vaccine-mediated protection

A

REDUCE or ELIMINATE virus replication after infection

36
Q

do memory T cells directly block infection

A

no, just reduce replication AFTER infection

37
Q

why can memory T cells be bad in some cases?

A

HIV may infect T cells so virus cannot be recognized

38
Q

how do Ab levels change after each vaccine?

A

1st dose: increases, then declines
2nd dose: increases even higher but declines
3rd dose: increases even more, then declines a bit

39
Q

what is immune imprinting?

A

impact of viral infection or vaccination on FUTURE patterns of Ab responses when re-exposed to distinct variants of the original antigen

40
Q

another name for immune imprinting

A

original antigenic sin

41
Q

result of immune imprinting

A

upon infection with antigen that is a variant of previous antigen, immune system will re-activate original Ab but won’t be able to target this new variant

42
Q

effect of immune imprinting on COVID

A

COVID continues to evolve so if someone keeps receiving the same vaccine, will make pools of Ab that are effective against the original virus only

43
Q

how to overcome immune imprinting?

A

trick immune system to recognize new variant with multiple doses

44
Q

what is antibody-dependent enhancement? what virus does this occur with?

A

1st DENV infection: mild symptoms

2nd DENV infection: severe, fatal symptoms

45
Q

how does antibody-dependent enhancement work?

A

existing Ab bind virus and help it infect macrophages (DENV target) to enhance infection

46
Q

2 broad ways to make a vaccine

A
  1. use pathogen (inactivated or attenuated)
  2. special design
47
Q

benefit and downside of attenuated and inactivated virus vaccine

A

benefit: high protection efficacy

downside: high risk

48
Q

2 benefits of subunit vaccine

A

low immunogenicity and low risk

49
Q

how can we enhance immunogenicity in subunit vaccines?

A

formulation with ADJUVANT

50
Q

what is the role of adjuvants?

A

protect immunogens from degradation in vivo and enhance targeting to DCs for stronger immune response

51
Q

4 licensed adjuvants and vaccines they are in

A
  1. Aluminum OH (HBV, tetanus)
  2. MF59 (influenza)
  3. AS04 (GSK HPV)
  4. Toxoids (Haemophilus influenza type b)
52
Q

what is MF59?

A

squalene droplets combined with 2 surfactants

53
Q

what is AS04?

A

aluminum and bacterial lipid

54
Q

3 criteria for successful vaccine?

A
  1. safety
  2. protective efficacy
  3. cost
55
Q

before COVID, how long did it take to develop vaccine?

A

10-15 years

56
Q

what is the estimated cost for developing vaccines?

A

$500-800 million

57
Q

why is high vaccine coverage required (3)?

A
  1. acquire herd immunity
  2. reduce transmission
  3. protect vulnerable populations
58
Q

are most vaccines prophylactic or therapeutic?

A

prophylactic

59
Q

can vaccines be therapeutic rather than prophylactic?

A

some are therapeutic, given as post-exposure prophylaxis

60
Q

rabies vaccine as pre-exposure prophylaxis

A

3 doses given to ppl at high risk for contracting rabies

61
Q

rabies vaccine as post-exposure prophylaxis

A

5 doses given to ppl exposed to suspected or confirmed rabid animals

given with rabies immunoglobulin

62
Q

3 human pathogenic viruses without vaccines

A
  1. HSV
  2. HIV
  3. HCV
63
Q

7 methods for HIV vaccine

A
  1. whole inactivated
  2. live attenuated
  3. synthetic peptides
  4. recombinant subunit
  5. DNA
  6. recombinant bacterial vectors
  7. recombinant viral vectors
64
Q

3 barriers towards successful HIV vaccines

A
  1. high diversity of HIV subtypes and strains
  2. undefined correlates of protective immunity –> i.e. don’t know what will help protect
  3. lack of reliable animal model to test vaccine candidates
65
Q

3 criteria for effective HIV vaccine

A
  1. induce broadly neutralizing Ab
  2. induce cytotoxic T cell response in most ppl
  3. induce strong mucosal immune responses
66
Q

4 types of COVID vaccines

A
  1. mRNA
  2. AAV
  3. Subunit
  4. Inactivated virus vaccine

MIMM 324 (37 decks)

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